This dataset contains MRI data and Imaris modeling analysis of CLARITY-cleared, immunostained tissue associated with a study that assessed the effects of lipid blends containing various levels of a hydrolyzed fat system on myelin development in healthy neonatal piglets. Data are from thirty-two piglets of mixed sexes across four diet treatment groups and includes a sow-fed reference group. MRI data (presented in Figure 2 of the associated article) consists of volumetric data from Voxel-Based Morphometry analysis in brain grey matter and white matter, as well as mean fractional anisotropy and mean orientation dispersion index data from Tract-Based Spatial Statistics analysis. Imaris data (presented in Figure 3 of the associated article) consists of twenty-one select output measures from 3D modeling analysis of PLP-stained prefrontal cortex tissue. All methods used for collection/generation/processing of data are described in the associated article: Louie AY, Rund LA, Komiyama-Kasai KA, Weisenberger KE, Stanke KL, Larsen RJ, Leyshon BJ, Kuchan MJ, Das T, Steelman AJ. A hydrolyzed lipid blend diet promotes myelination in neonatal piglets in a region and concentration-dependent manner. J Neurosci Res. 2023.